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J Immunol. 2016 May 15;196(10):4185-95. doi: 10.4049/jimmunol.1600014. Epub 2016 Apr 13.

Variable Major Proteins as Targets for Specific Antibodies against Borrelia miyamotoi.

Author information

1
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
2
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands;
3
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520;
4
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands;
5
Center for Infectious Disease Control, National Institute for Public Health and the Environment, 3720 BA Bilthoven, the Netherlands;
6
Central Research Institute of Epidemiology, Moscow 111123, Russia;
7
Izhevsk State Medical Academy, Izhevsk 426034, Russia; and.
8
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
9
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; lyme@amc.uva.nl.

Abstract

Borrelia miyamotoi is a relapsing fever spirochete in Ixodes ticks that has been recently identified as a human pathogen causing hard tick-borne relapsing fever (HTBRF) across the Northern Hemisphere. No validated serologic test exists, and current serologic assays have low sensitivity in early HTBRF. To examine the humoral immune response against B. miyamotoi, we infected C3H/HeN mice with B. miyamotoi strain LB-2001 expressing variable small protein 1 (Vsp1) and demonstrated that spirochetemia was cleared after 3 d, coinciding with anti-Vsp1 IgM production. Clearance was also observed after passive transfer of immune sera to infected SCID mice. Next, we showed that anti-Vsp1 IgG eliminates Vsp1-expressing B. miyamotoi, selecting for spirochetes expressing a variable large protein (VlpC2) resistant to anti-Vsp1. The viability of Asian isolate B. miyamotoi HT31, expressing Vlp15/16 and Vlp18, was also unaffected by anti-Vsp1. Finally, in nine HTBRF patients, we demonstrated IgM reactivity to Vsp1 in two and against Vlp15/16 in four ∼1 wk after these patients tested positive for B. miyamotoi by PCR. Our data show that B. miyamotoi is able to express various variable major proteins (VMPs) to evade humoral immunity and that VMPs are antigenic in humans. We propose that serologic tests based on VMPs are of additional value in diagnosing HTBRF.

PMID:
27076681
PMCID:
PMC5008243
DOI:
10.4049/jimmunol.1600014
[Indexed for MEDLINE]
Free PMC Article

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